-
Seediscussions,stats,andauthorprofilesforthispublicationat:http://www.researchgate.net/publication/235925375
FunctionalRecoveryEnhancementFollowingInjurytoRodentPeronealNervebyLionsManeMushroom,Hericiumerinaceus(Bull.:Fr.)Pers.(Aphyllophoromycetideae)DATASETinINTERNATIONALJOURNALOFMEDICINALMUSHROOMSMARCH2013ImpactFactor:1.12DOI:10.1615/IntJMedMushr.v11.i3.20
CITATIONS13
DOWNLOADS220
VIEWS243
7AUTHORS,INCLUDING:
WongKahHuiUniversityofMalaya34PUBLICATIONS205CITATIONS
SEEPROFILE
NoorlidahAbdullahUniversityofMalaya119PUBLICATIONS505CITATIONS
SEEPROFILE
UmahRaniKuppusamyUniversityofMalaya96PUBLICATIONS710CITATIONS
SEEPROFILE
VikineswarySabaratnamUniversityofMalaya184PUBLICATIONS950CITATIONS
SEEPROFILE
Availablefrom:WongKahHuiRetrievedon:24July2015
-
225
International Journal of Medicinal Mushrooms, 11(3):225236
(2009)
1521-9437/09/$35.00 2009 by Begell House, Inc.
Functional Recovery Enhancement Following Injury to Rodent
Peroneal Nerve by Lions Mane Mushroom, Hericium erinaceus (Bull.:
Fr.) Pers. (Aphyllophoromycetideae)
Kah-Hui Wong,1 Murali Naidu,2 Rosie Pamela David,2 Mahmood Ameen
Abdulla,3 Noorlidah Abdullah,1 Umah Rani Kuppusamy,3 &
Vikineswary Sabaratnam1,*1Institute of Biological Sciences, Faculty
of Science; 2Department of Anatomy, Faculty of Medicine;
3Depart-ment of Molecular Medicine, Faculty of Medicine, University
of Malaya, 50603 Kuala Lumpur, Malaysia
* Address all correspondence to Vikineswary Sabaratnam,
Institute of Biological Sciences, Faculty of Science, University of
Malaya, 50603 Kuala Lumpur, Malaysia; Tel.: +603-79674349; Fax:
+603-79674178; [email protected]
ABSTRACT: Peripheral nerve injury represents a huge burden to
society. Following peripheral nerve injury, improved behavioral
outcome may be the most important evidence of functionality of
axonal regeneration after any repair strategy. Nerve-crush injury
is a well-established axonotmetic model in experimental
regeneration studies to investigate the impact of various
pharmacological treatments. Hericium erinaceus is a temperate
mushroom but is now being cultivated in tropical Malaysia. In this
study, we investigated the activity of aqueous extract of H.
erinaceus fresh fruitbodies in promoting functional recovery
following an axonotmetic peroneal nerve injury in adult female
Sprague-Dawley rats with a long-term view toward the possible use
of this mushroom in the treatment of nerve injury. Functional
recovery was assessed in the behavioral experiment by walking-track
analysis and toe-spreading refl ex. The peroneal functional index
(PFI) was determined before surgery and after sur-gery, as the rats
showed signs of recovery. Analysis of the PFI indicated that the
return of hind-limb function occurred by day 10 to 14 and by day 14
to 17 in the treated and control (nontreated) groups, respectively.
Normal toe-spreading in the crushed limb was achieved by day 7 to
10 and day 12 to 17 in the treated and control group, respectively.
These results suggest that daily administration of aqueous extract
of H. erinaceus fresh fruitbodies has a benefi cial effect on the
recovery of injured rat peroneal nerve in the early stages of
regeneration. The PFI and toe-spreading refl ex improved faster in
the treated group than in the nontreated group.
KEY WORDS: Hericium erinaceus, functional recovery, peripheral
nerve, crush injury, peroneal functional index, toe-spreading refl
ex, medicinal mushrooms
ABBREVIATIONS
E: experimental; DHEA: dehydroepiandrosterone; EDL: the extensor
digitorum longus; MnSOD: manganese super-oxide dismutase; N:
normal; NGF: nerve growth factor; PFI: peroneal functional index;
PLF: print length factor; SFI: sciatic functional index; TFI:
tibial functional index; TSF: toe-spread factor.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
226 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
I. INTRODUCTION
Medicinal properties of Hericium erinaceus (Bull.: Fr.) Pers.
(also known as Lions Mane, Monkeys Head, Hedgehog Fungus, Satyrs
Beard, Pom Pom Blanc, Igelstachelbart, and Yamabushitake), Hericia
ceae, Aphyllophoromycetideae have been well-known for hundreds of
years in traditional Chinese and Japanese cooking and herbal
medicine to treat various human diseases, and hot aqueous extracts
from dried fruitbodies are used as a health drink called Houtou.
The fruitbodies are com-posed of numerous constituents, such as
polysac-charides,1 proteins,1 lectin,2 and hericenones.35
A study carried out at the Third Peoples Hospital of Shanghai
showed that H. erinaceus, in tablet form, was effective in treating
ulcers, infl am-mations, and tumors of the alimentary canal.6 The
cytoprotective effect of H. erinaceus freeze-dried fruitbodies
against ethanol-induced gastric mucosal injury in rats was
investigated. The rats had less gastric-mucosal damage, decreased
edema, and no submucosal leucocyte infi ltration when compared to
nontreated rats.7
The most promising activity of H. erinaceus is the stimulation
of nerve growth factor (NGF) synthesis by hericenones from
fruitbodies35 and erinacines from mycelium.813 An
exopolysaccha-ride derived from H. erinaceus promotes neuronal
differentiation and survival.14 Neurotrophic activi-ties derived
from dried fruitbodies of H. erinaceus have also been studied in
rat hippocampal slice neurons.15,16 Our previous study has shown
that aqueous extracts of this mushroom grown in a tropi-cal
environment could stimulate neurite outgrowth of the cultured cells
of the neural hybrid clone NG108-15.17 These fi ndings prove that
H. erina-ceus may have the potential to stimulate neurons to regrow
in the treatment of senility and Alzheimers disease, and for
repairing neurological trauma from strokes, improving muscle or
motor response path-ways, and increasing cognitive function.
Peripheral nerve problems are common and encompass a wide
spectrum of traumatic injuries, diseases, tumors, and iatrogenic
lesions. The inci-dence of traumatic injuries is estimated as more
than 500,000 new patients annually.18 Injuries to peripheral nerves
result in partial or total loss of
motor, sensory, and autonomic functions in the involved segments
of the body. Reinnervation of denervated targets can be achieved by
the regenera-tion of injured axons or by collateral branching of
undamaged axons in the surrounding.18
Common types of experimentally induced injuries include crush
injury that causes axonal interruption but preserves the connective
sheaths (axonotmesis), complete transection disrupting the whole
nerve trunk (neurotmesis), and resection of a nerve segment
inducing a gap of certain length. Nerve-crush injury is a
well-established model in experimental regeneration studies to
investigate the impact of various pharmacological treatments.1824
It is known that after the injury due to the tissue destruction,
free-oxygen radicals increase and cause tissue damage.2528
Rodents, particularly the rat and mouse, have become the most
frequently utilized animal mod-els for the study of peripheral
nerve regeneration because of the widespread availability of these
animals as well as the distribution of their nerve trunks, which is
similar to humans.18,29 Gutmann and Guttmann30 demonstrated that
the loss of ability to spread the toes of the hind limb is a
reliable parameter for the evaluation of the extent of injury to
the sciatic nerve and for monitoring the recovery. However, the
method proposed was quite rudimentary and did not allow the
quantifi ca-tion of any parameter. A reliable and reproducible
quantitative method for the assessment of functional condition,
known as the sciatic function index (SFI), was introduced by De
Medinaceli et al.31 They designed a quantitative method of
analyzing hind-limb performance by examining footprints based on
several measurements of the footprints made on X-ray fi lm. Carlton
and Goldberg32 introduced the tibial functional index (TFI) and the
peroneal functional index (PFI), which were later modifi ed by Bain
et al.33 The use of walking-track analysis has been widely used in
the rat sciatic nerve stud-ies and is considered as an assessment
of global function recovery.3234
Research on the medicinal value of H. erinaceus grown in
Malaysia, a tropical country, is minimal and yet to be explored. To
our knowledge, no information is available on the nerve
regeneration and repair property of the locally grown mushroom
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
Volume 11, Issue 3, 2009 227
FUNCTIONAL RECOVERY ENHANCEMENT FOLLOWING INJURY BY HERICIUM
ERINACEUS
H. erinaceus. Therefore, the aim of this study was to assess the
peroneal nerve regeneration activity of aqueous extract of H.
erinaceus fresh fruitbod-ies in adult female Sprague-Dawley rats
after crush injury. Functional recovery was assessed in behavioral
experiments by walking-track analysis and toe-spreading refl
ex.
II. MATERIALS AND METHODS
A. Preparation of Aqueous Extracts and Animal Grouping
H. erinaceus fresh fruitbodies were obtained from a mushroom
farm in Tanjung Sepat, Selangor, Malaysia. Fresh fruitbodies were
boiled with distilled water at a ratio of 1:1 for 30 minutes with
agitation, left covered for 30 minutes, cooled and fi ltered. The
use of rats was approved by the Animal Care and Use Committee of
the Faculty of Medicine, University of Malaya, Approval Number
ANA/16/03/2007/MDKN(R). Twenty adult female Sprague-Dawley rats
weighing 180200 g were randomly assigned to two groups. The control
group (n = 10) received daily oral administrations of distilled
water (10 mL/kg body weight/day), and the treatment group (n = 10)
received the aqueous extract of fresh fruitbodies (10 mL/kg body
weight/day) for 14 days to function as pretreatment before
surgery.
B. Surgical Procedure
On the 14th day, the rats were anesthetized with an
intraperitoneal injection of 3.5% chloral hydrate (10 mL/kg body
weight), then shaved and washed with antiseptic solution before
positioning for surgery. The right sciatic nerve and its two major
branches were exposed through a gluteal muscle-splitting incision.
A reliable and reproducible crush injury was created using a fi ne
watchmaker forceps no. 4 for 10 seconds on the peroneal nerve at 10
mm from the distal muscle, and complete crush was con-fi rmed by
the presence of a translucent band across the nerve (Fig. 1). The
incision was then closed in layers (muscle and skin) with
absorbable sutures. All operations were performed on the right
limb,
and the left limb served as an unoperated control. After closing
the incision with sutures, veterinary wound powder was applied to
the wounds. The extract or distilled water was continuously fed for
another 20 days. All rats were observed for general well-being and
had ad libitum access to food and water throughout the study.
C. Functional Assessment of Limb Recovery
1. Walking-Track Analysis
The rats were allowed conditioning trials in a walk-ing track
(8.2 42 cm) darkened at one end. White offi ce paper cut to the
appropriate dimensions was placed on the bottom of the track. The
rats hind limbs were dipped in Chinese ink, and the rat was
permitted to walk down the track, leaving its hind footprints on
the paper (Fig. 2). Footprints were obtained before surgery (day 0)
and on day 4, 7, 10, and 14 after surgery, as the rats showed signs
of recovery.
Several trials are required to obtain the most representative
prints for analysis.33,34 In the be-ginning, they often stop to
explore the corridor; thereafter, they walk steadily to the
darkened cage.31 The rat may stand up, putting all its weight onto
its rear legs and creating untypically long print length (Fig. 3A).
Some prints were unmeasurable due to smearing of the print,
dragging of the tail
FIGURE 1. Complete crush of peroneal nerve is con-fi rmed by the
presence of a translucent band (as indicated by an arrow) across
the nerve.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
228 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
across the print, or contamination with front paw prints (Fig.
3B).
PFI is based on multiple linear regression analyses of factors
derived from measurements of walking tracks in rats with peroneal
nerve injury. The factors that contributed to PFI were print length
factor (PLF) and toe-spread factor (TSF). Paired measurements of
the print length (distance from heel to toe) (PL) and the
toe-spread (distance from the fi rst to fi fth toes) (TS) were
taken for the unoperated/normal (N) foot and the correspond-ing
operated/experimental (E) foot.33 A factor was generated from each
of the measurements of the walking track by subtracting the normal
from the experimental value and dividing this difference by the
normal measurement:
EPL-NPLPrint length factor (PLF) =
NPL
ETS-NTSToe-spread factor (TSF) =
NTS
The multiple linear regression analysis per-formed between the
peroneal nerve defi cit and the factors from the walking tracks
gave the equation for PFI.
EPL-NPL ETS-NTSPFI = 174.9 80.3 13.4
NPL NTS
The PFI oscillates around 0 to 10 for normal nerve function, and
around 100 for total dys-function, such as would result from a
complete transection of the sciatic nerve.35 A complete recovery of
function was determined when the PFI for each group plateaued or
returned to its presurgery value.
2. Toe-Spreading Refl ex
The rats were inspected everyday after surgery. During these
inspections, each rat was held by its tail above a surface and
lowered towards it and carefully observed for a minute or two.36
Activities were classifi ed according to the toe-spreading refl ex
of the affected right hind limb: 0, no spreading; 1, minimal
spreading; 2, average spreading; 3, normal spreading. The rate of
peroneal nerve regeneration was calculated by dividing the distance
of the crushing site from the distal muscle (10 mm) by the day
normal spreading is achieved.
D. Statistical Analysis
The means of the data were subjected to a one-way analysis of
variance (ANOVA) and the signifi cance of the difference between
the means was determined by the Duncans multiple-range tests at 95%
least-signifi cant difference (p < 0.05).
III. RESULTS AND DISCUSSION
No rats in the two groups showed any sign of in-fection or foot
ulceration at any time throughout
FIGURE 2. Walking-track apparatus. Rat in an 8.2 42 cm
walking-track apparatus lined with white offi ce paper. After the
hind limbs of the rat are dipped in Chinese ink, the rat walks
towards the darkened end of the corridor.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
Volume 11, Issue 3, 2009 229
FUNCTIONAL RECOVERY ENHANCEMENT FOLLOWING INJURY BY HERICIUM
ERINACEUS
the experiment. Normal gait was recorded as the hind-limb toes
fully spread in each group before surgery. Crush injury to the
peroneal nerve results in paralysis of the extensor digitorum
longus (EDL) muscle. Flexion contracture (drop foot), as shown in
Figure 4, was observed due to the lack of dorsal fl exion of the
ankle. The rats tend to drag the dorsum of their foot until
reinnervation of the EDL muscle.
The clinically relevant outcome is end-organ functional
recovery, which is the ultimate test of nerve regeneration.37
Functional evaluation showed that recovery in the treated group
began on day 4, whereas the crushed limb in the control group
remained dysfunctional. Rats in the control group showed
clumping of toes and dragging of the injured foot (Fig. 5A). These
rats are recorded as having unmeasurable walking tracks. On the
other hand, the treated group demonstrated toe-spreading and clear
footprints on the walking tracks (Fig. 5B).
Analysis of PFI, as shown in Table 1, indicated that the return
of hind-limb function occurred by 14 or 17 days after surgery in 5
rats each of control group. Rats treated with aqueous extract of
fresh fruitbodies experienced return of function by 10 and 14 days
after surgery in 8 rats and 2 rats, respec-tively. When the groups
mean PFI were compared at each time interval, the mean PFI of the
treated
FIGURE 3. Unmeasurable walking tracks. (A) Long print length as
indicated by arrows when a rat stands up and puts all its weight
onto its hind limbs. (B) Contamination with front paw prints as
indicated by arrows.
(B)(A)
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
230 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
FIGURE 4. Gait changes associated with peroneal nerve
injuryjoint contracture, making measurement impossible because the
rat walks on the dorsum of the affected foot. Arrow indicates the
operated limb.
(Fig. 5Ai) (Fig. 5Aii)
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
Volume 11, Issue 3, 2009 231
FUNCTIONAL RECOVERY ENHANCEMENT FOLLOWING INJURY BY HERICIUM
ERINACEUS
rats was signifi cantly less than the control group on day 0, 7,
10, and 14 (p < 0.05). Print length is shorter at fi rst33 and
will increase back to normal with time or as functional recovery
takes place.
With regard to the toe-spreading refl ex (Table 2), normal
spreading appeared between 12 (1 rat), 13 (2 rats), 15 (2 rats),
and 17 days (5 rats) after surgery in the control group. However,
in the treated group, the defi cit completely disappeared 7 (3
rats), 9 (2 rats), and 10 days (5 rats) after surgery. The rate of
peroneal nerve regeneration was almost twofold higher in the
treated group compared to the control group (p < 0.05). Figure 6
shows minimal toe-spreading on the right limb in the control group
and normal toe-spreading in the treated group 7 days after surgery.
Thus, the treated rats showed
a faster recovery of the toe-spreading refl ex when compared to
the controls.
Gait and walking-track analysis have been used clinically, both
to describe lower limb nerve defi -cits and to assess function. The
hind-limb function served by the sciatic nerve and its branches in
the rat can be quantitatively, reliably, and easily assessed by
gait analysis through footprints.33 This method is simple to
perform, with minimal discomfort to the rat.38 Furthermore,
walking-track analysis is a direct measurement of function, whereas
electro-physiologic and morphometric histologic analyses are
indirect methods that may not necessarily cor-relate with
functional outcome.39
The recovery of a muscle is a very complex and prolonged
process. It sets in with the innerva-
(Fig. 5Bi) (Fig. 5Bii)
FIGURE 5. Walking tracks of footprints after 4 days of right
peroneal nerve-crush injury. Arrows indicate footprints of the
operated limb. (Ai) and (Aii) Footprints in control groupdistilled
water (10 mL/kg body weight per day). The palsy after interruption
of the peroneal nerve is characterized by fl exion contracture of
the paws (drop foot), absence of toe-spreading refl ex, and some
dragging of the operated limb. (Bi) and (Bii) Footprints in
treatment groupaqueous extract of Hericium erinaceus fresh
fruitbodies (10 mL/kg body weight per day). Toe-spreading and clear
footprints of the operated limb are demonstrated on the walking
tracks.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
232 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
tion of the muscle by the fi rst regenerating fi bers. This
stage is a necessary preliminary to recovery, but must not be
identifi ed with the recovery of the muscle as a functioning
entity.36 The process of recovery is not complete with the fi rst
return of a movement. The degree of movement, indicated by the
toe-spreading refl ex in the experiment described, increases for
some time. Even after the full extent of movement has returned, the
regeneration is still incomplete because the muscle continues for
some weeks to increase in weight, the rate of increase presumably
depending on the amount of use of the limb. Moreover, the nerve fi
bers themselves continue to increase in diameter for many months
after functional recovery is apparently complete.36 Recovery
proceeds more slowly with greater dis-tance between lesion and end
organ.
Peripheral nerves may be subjected to crush injuries in a
variety of circumstances, including motor vehicle accidents,
fractures, dislocations, and natural disasters such as
earthquakes.40 In crush injury or second-degree Sunderland injury,
there is an interruption of the nerves axons, with subsequent
Wallerian degeneration distal to the site of injury. The
degenerative products are eliminated by the cooperative action of
denervated Schwann cells and infi ltrating macrophages. After this
type of injury, the continuity of the endoneurial sheath is
preserved, providing the necessary guidance for regenerating axons
from the proximal nerve stump to their peripheral targets.41,42
Axonal regenera-tion requires an adequate substrate of trophic and
tropic factors, provided by reactive Schwann cells, macro phages,
and the extracellular matrix within
TABLE 1Return of Function Following Crush Injury to the Peroneal
Nerve as Shown by Peroneal Functional Index (PFI). PFI of Rats
Treated with Aqueous Extract of Hericium erinaceus Fresh
Fruitbodies Returned to Presurgery Values 4 to 7 Days Earlier Than
Controls
PFI values
Group Day 0 Day 4 Day 7 Day 10 Day 14 Day 17
Control 15.63 4.21a Unmeasurable due to 50.36 7.13a 32.71 5.27a
21.52 8.88a 18.88 6.14 dragging of operated foot
Treatment 10.01 3.40b 52.88 12.34 21.44 5.56b 11.30 4.49b 10.71
2.43b
Note: Values on day 0 are before surgery. Data are expressed as
means standard deviation (n = 10 for day 0, 7, and 10 in both
groups, day 4 in treatment group, day 14 in control group; n = 2
for day 14 in treatment group; n = 5 for day 17 in control group).
Means with different letters in the same column are signifi cantly
different (p < 0.05, one-way analysis of variance/ANOVA).
TABLE 2Recovery of Toe-Spreading Following Crush Injury to the
Peroneal Nerve. Toe-Spreading of Rats Treated with Aqueous Extract
of Hericium erinaceus Fresh Fruitbodies Returned to Normal
Spreading 5 to 10 Days Earlier than Controls
Number of rats with normal spreading
Rate of peroneal nerve regenerationGroup Day 7 Day 8 Day 9 Day
10 Day 11 Day 12 Day 13 Day 14 Day 15 Day 16 Day 17 (mm/day)
Control 0 0 0 0 0 1 3 3 5 5 10 0.66 0.09a
Treatment 3 3 5 10 10 10 10 10 10 10 10 1.15 0.20b
Note: n = 10 for both groups. Means with different letters in
the last column are signifi cantly different (p < 0.05, one-way
analysis of variance/ANOVA).
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
Volume 11, Issue 3, 2009 233
FUNCTIONAL RECOVERY ENHANCEMENT FOLLOWING INJURY BY HERICIUM
ERINACEUS
the degenerated nerve. From a clinical perspective, in
second-degree Sunderland lesions, function will be almost
completely restored, although the process requires many
months.43
Functional deterioration following crush injury is not only
related to the impact of the crush itself but also includes other
important components, such as ischemia of the limb. Li et al.44
suggested that the treatment of deferoxamine, an antioxidant,
reduces ischemia or reperfusion injury after nerve compression.
They hypothesized that therapeutic intervention with antioxidants
protects the nerve from ischemia or reperfusion injury and yields a
quick recovery from peripheral nerve compression injury. Studies on
crush-injury models in peripheral nerves have shown better
functional recovery when therapies were directed against
ischemia-reperfusion injury by using antioxidants, lipid
peroxidation inhibitors, and anti-infl ammatory agents.24,44
The antioxidant and free-radical scavenging properties of
mushrooms have been reported. Pos-sible protective roles of
antioxidant and free-radical scavenging properties of mushrooms are
due to their ability to capture metals, inhibit lipoxygenase, and
scavenge-free radicals.45,46 H. erinaceus, a temperate mushroom, is
now successfully grown in tropical conditions and has been reported
to possess anti-oxidant activity.47
With regard to its assumed mechanism of action, aqueous extract
of H. erinaceus fresh fruitbodies may act directly or indirectly by
modifying the action of neurotrophic factors. Neurotrophic fac-tors
or regeneration-promoting factors have been suggested to play an
essential role in the outcome of degeneration and regeneration
processes in the peripheral nervous system, both to ensure proper
innervation of the target tissues and to improve re-myelination.48
The improved regeneration observed after aqueous extract treatment
may be related either to direct neurotrophic factor-like activity
or to the promotion of the effects of nerve-derived neurotrophic
factors.
Anti-infl ammatory drugs such as methylpredni-sone,
pregnenolone, and indomethacin have shown both experimental and
clinical enhancement of neural functional recovery following acute
spinal cord injuries.49 Gudemez et al.19 studied the ap-plication
of dehydroepiandrosterone (DHEA), a weak androgenic steroid,
immediately after crush injury. DHEA was shown to improve rat
sciatic nerve regeneration and prevent the development of a
secondary injury related to reperfusion. The
FIGURE 6. Recovery of toe-spreading refl ex after 7 days of
right peroneal nerve-crush injury. Arrows indicate the operated
limb. (A) Minimal toe-spreading on right limb in control
groupdistilled water (10 mL/kg body weight per day). (B) Normal
toe-spreading on right limb in treated groupaqueous extract of
Hericium erinaceus fresh fruitbodies (10 mL/kg body weight per
day).
(A)
(B)
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
234 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
study was confi rmed by the improved gait pattern of
DHEA-treated rats, as measured by SFI, which returned to normal
values faster than the control group. Lymphotoxin or tumor necrosis
factor- is a glycoprotein produced by activated T and B
lym-phocytes. It can enhance motor-function recovery of the crushed
sciatic nerve in the early stages of regeneration. The mechanism of
protection could be related to its ability to induce the synthesis
of manganese superoxide dismutase (MnSOD), a mito chondrial enzyme
involved in detoxifi cation of superoxide radicals.24 On the other
hand, Al-Bishri et al.50 also showed that the preoperative
admin-istration of the steroid bethamethasone improved the
functional recovery of the rat sciatic nerve, as measured by the
toe-spreading ability.
By taking natural products into consideration, the repair effect
of the traditional Chinese medicinal herb Achyranthes bidentata
root aqueous extract on the regeneration of the crushed common
peroneal nerve in rabbits was studied by Ding et al.51 by using a
combination of electrophysiological assess-ment and histological
investigation. The root extract could accelerate peripheral nerve
regeneration in a dose-dependent manner.
Data obtained from this study suggest that daily treatment with
the aqueous extract of H. erinaceus fresh fruitbodies provides a
quicker recovery of function than no treatment at all. Because the
ex-tract administration increases the rate of recovery from
peripheral nerve injury, patients who receive H. erinaceus may
experience a more expeditious improvement in their quality of life
and more complete functional recovery after injury.
IV. CONCLUSIONS
After peroneal nerve-crush injury, functional re-covery was
enhanced in rats treated with aqueous extract of H. erinaceus fresh
fruitbodies, as assessed in behavioral experiments by walking-track
analysis and toe-spreading refl ex. Therefore, H. erinaceus could
be a good candidate in facilitating functional recovery after
peripheral nerve injury. However, prior to the application of the
mushroom by the nutraceutical industry, the identifi cation of
the
active compounds and the mechanisms by which these may treat or
protect against nerve injury are highly warranted.
ACKNOWLEDGMENTS
The authors would like to thank the Ministry of Science,
Technology and Innovation, Malaysia, (MOSTE) for grant
12-02-03-2050 and the Univer-sity of Malaya for the research grants
FR129/2007A and PS150/2008B. The technical assistance by Dr. Mohd.
Hairulhisyam Ngatiman, Mrs. Robiah Bakar, Mrs. Chang May Hing, the
staff of the Department of Anatomy, and Animal House is greatly
appreciated.
REFERENCES
1. Mizuno T. Bioactive substances in Hericium erinaceus (Bull.:
Fr.) Pers. (Yamabushitake), and its medicinal utilization. Int J
Med Mushr. 1999;1:10519.
2. Kawagishi H, Mori H, Uno A, Kimura A, Chiba S. A sialic
acid-binding lectin from the mushroom Hericium erinaceus. FEBS
Lett. 1994;340:568.
3. Ueda K, Tsujimori M, Kodani S, Chiba A, Kubo M, Masuno K,
Sekiya A, Nagai K, Kawagishi H. An en-doplasmic reticulum (ER)
stress-suppressive compound and its analogues from the mushroom
Hericium erina-ceus. Bioorg Med Chem. 2008;16:946770.
4. Kawagishi H, Ando M, Shinba K, Sakamoto H, Yoshida S,
Ishiguro Y, Furukawa S. Chromans, hericenones F, G and H from the
mushroom Hericium erinaceus. Phytochemistry. 1993;32:1758.
5. Kawagishi H, Ando M, Sakamoto H, Yoshida S, Ojima F, Ishiguro
Y, Ukai N, Furukawa S. Hericenones C, D and E, stimulators of nerve
growth factor (NGF)-synthesis, from the mushroom Hericium
erinaceus. Tetrahedron Lett. 1991;32:45614.
6. Chen GL. Studies on the cultivation and medicinal effi cacy
of Hericium erinaceus. Shanghai (P R China): The Edible Fungus
Research Institute of the Shanghai Academy of Agricultural Science;
1992.
7. Abdulla MA, Mohd Noor S, Sabaratnam V, Abdullah N, Wong KH,
Mohd Ali H. Effect of culinary-medicinal lions mane mushroom,
Hericium erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae), on
ethanol-induced gas-tric ulcers in rats. Int J Med Mushr.
2008;10:32530.
8. Kawagishi H, Masui A, Tokuyama S, Nakamura T. Erinacines J
and K from the mycelia of Hericium eri-naceus. Tetrahedron.
2006;60:84636.
9. Lee EW, Shizuki K, Hosokawa S, Suzuki M, Suganuma H, Inakuma
T, Li J, Ohnishi-Kameyama M, Nagata T,
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
Volume 11, Issue 3, 2009 235
FUNCTIONAL RECOVERY ENHANCEMENT FOLLOWING INJURY BY HERICIUM
ERINACEUS
Furukawa S, Kawagishi H. Two novel diterpenoids, erinacines H
and I from the mycelia of Hericium erina-ceus. Biosci Biotechnol
Biochem. 2006;64:24025.
10. Shimbo M, Kawagishi H, Yokogoshi H. Erinacine A increases
catecholamine and nerve growth factor con-tent in the central
nervous system of rats. Nutr Res. 2005;25:61723.
11. Kawagishi H, Shimada A, Shizuki K, Mori H, Okamoto K,
Sakamoto H, Furukawa S. Erinacine D, a stimula-tor of
NGF-synthesis, from the mycelia of Hericium erinaceus. Heterocycl
Commun. 1996;2:514.
12. Kawagishi H, Shimada A, Hosokawa S, Mori H, Sakamoto H,
Ishiguro Y, Sakemi S, Bordner J, Kojima N, Furukawa S. Erinacines
E, F, and G, stimulators of nerve growth factor (NGF)-synthesis,
from the mycelia of Hericium erinaceus. Tetrahedron Lett.
1996;37:7399402.
13. Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F,
Sakamoto H, Ishiguro Y, Furukawa S. Erinacines A, B and C, strong
stimulators of nerve growth factor (NGF)-synthesis, from the
mycelia of Hericium erina-ceus. Tetrahedron Lett.
1994;35:156972.
14. Park YS, Lee HS, Won MH, Lee JH, Lee SY, Lee HY. Effect of
an exo-polysaccharide from the culture broth of Hericium erinaceus
on enhancement of growth and differentiation of rat adrenal nerve
cells. Cytotechnology. 2002;39:55162.
15. Moldavan MG, Grygansky AP, Kirchoff B. Hericium erinaceus
(Bull.: Fr.) Pers. extracts effect on the neu-rons impulse activity
in stratum pyramidale of zone CA1 hippo campal slices in rats.
Third International Conference on Mushroom Biology and Mushroom
Products; 1999 Oct 1216; Sydney, Australia.
16. Grygansky AP, Moldavan MG, Kolotushkina O, Kirchhoff B,
Skibo GG. Hericium erinaceus (Bull.: Fr.) Pers. extract effect on
nerve cells. Int J Med Mushr. 2001;3:152.
17. Wong KH, Sabaratnam V, Abdullah N, Naidu M, Keynes R.
Activity of aqueous extracts of lions mane mushroom Hericium
erinaceus (Bull.: Fr.) Pers. (Aphyllophoromycetideae) on the neural
cell line NG108-15. Int J Med Mushr. 2007;9:5765.
18. Rodriguez FJ, Valero-Cabr A, Navarro X. Regeneration and
functional recovery following peripheral nerve in-jury. Drug Disc
Today: Dis Models. 2004;1:17785.
19. Gudemez E, Ozer K, Cunningham B, Siemionow K, Browne E,
Siemionow M. Dehydroepiandrosterone as an enhancer of functional
recovery following crush injury to rat sciatic nerve. Microsurgery.
2002;22:23441.
20. Islamov RR, Hendricks WA, Jones RJ, Lyall GJ, Spanier NS,
Murashov AK. 17Beta-estradiol stimulates regeneration of sciatic
nerve in female mice. Brain Res. 2002;943:2836.
21. Paydarfar JA, Paniello RC. Functional study of four
neurotoxins as inhibitors of post-traumatic nerve re-generation.
Laryngoscope. 2001;111:84450.
22. Lee BH, Won R, Baik EJ, Lee SH, Moon CH. An ani-mal model of
neuropathic pain employing injury to the sciatic nerve branches.
Neuroreport. 2000;11:65761.
23. Al Moutaery K, Arshaduddin M, Tariq M, Al Deeb S. Functional
recovery and vitamin E level following sciatic nerve crush injury
in normal and diabetic rats. Int J Neurosci. 1998;96:24554.
24. Algora J, Chen LE, Seaber AV, Wong GH, Urbaniak JR.
Functional effects of lymphotoxin on crushed peripheral nerve.
Microsurgery. 1996;17:1315.
25. Arslan E, Milcan A, Unal S, Demirkan F, Polat A, Bagdatoglu
O, Aksoy A, Polat G. The effects of carni-tine on distally-burned
dorsal skin fl ap: an experimental study in rats. Burns.
2003;29:2217.
26. Cinel I, Avlan D, Cinel L, Polat G, Atici S, Mavioglu I,
Serinol H, Aksoyek S, Oral U. Ischemic preconditioning reduces
intestinal epithelial apoptosis in rats. Shock. 2003;19:58892.
27. Bagdatoglu C, Saray A, Surucu HS, Ozturk H, Tamer L. Effect
of trapidil in ischemia/reperfusion injury of peripheral nerves.
Neurosurgery. 2002;51:21220.
28. Talas DU, Nayci A, Polat G, Atis S, Comelekoglu U,
Bagdatoglu OT, Bagdatoglu C. The effects of dexam-ethasone on lipid
peroxidation and nitric oxide levels on the healing of tracheal
anastomoses: an experimental study in rats. Pharmacol Res.
2002;46:26571.
29. Mackinnon SE, Hudson AR, Hunter DA. Histologic assessment of
the nerve regeneration in the rat. Plast Reconstr Surg.
1985;75:3848.
30. Gutmann E, Guttmann L. Factors affecting recovery of sensory
function after nerve lesions. J Neurol Psychiatry.
1942;5:11729.
31. De Medinaceli L, Freed WJ, Wyatt RJ. An index of the
functional condition of rat sciatic nerve based on measurements
made from walking tracks. Exp Neurol. 1982;77:63443.
32. Carlton JM, Goldberg NH. Quantitating integrated muscle
function following reinnervation. Surg Forum. 1986;37:6112.
33. Bain JR, Mackinnon SE, Hunter DA. Functional evaluation of
complete sciatic, peroneal, and posterior tibial nerve lesions in
the rats. Plast Reconstr Surg. 1989;83:12938.
34. Hare GMT, Evans PJ, Mackinnon SE, Best TJ, Bain JR, Szalai
JP, Hunter DA. Walking track analysis: a long term assessment of
peripheral nerve recovery. Plast Reconstr Surg. 1992;89:2518.
35. Varejo ASP, Cabrita AM, Patrcio JA, Bulaz-Cruz J, Gabriel
RC, Melo-Pinto P, Couto PA, Meek MF. Functional assessment of
peripheral nerve recovery in the rat: gait kinematics.
Microsurgery. 2001;21:3838.
36. Gutmann E. Factors affecting recovery of motor function
after nerve lesion. J Neurol Psychiatry. 1942;5:8195.
37. Chen B, Song Y, Liu Z. Promotion of nerve regeneration in
peripheral nerve by short-course FK506 after end-to-side
neurorrhaphy. J Surg Res. 2008;152:30310.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc
-
236 International Journal of Medicinal Mushrooms
K.-H. WONG ET AL.
38. Djikstra JR, Meek MF, Robinson PH, Gramsbergen A. Methods to
evaluate functional nerve recovery in adult rats: walking track
analysis, video analysis and the with-drawal refl ex. J Neurosci
Methods. 2000;96:8996.
39. Dellon AL, Mackinnon SE. Selection of the appropriate
parameter to measure neural regeneration. Ann Plast Surg.
1989;23:197202.
40. Chen LE, Seaber AV, Glisson RR, Davies H, Murrell GA,
Anthony DD, Urbaniak JR. The functional recov-ery of peripheral
nerves following defi ned acute crush injuries. J Orthop Res.
1992;10:65764.
41. Seddon H. Three types of nerve injury. Brain.
1943;66:23788.
42. Sunderland S. The anatomy and physiology of nerve injury.
Muscle Nerve. 1990;13:77184.
43. Varejo ASP, Cabrita AM, Meek MF, Bulaz-Cruz J, Filipe VM,
Gabriel RC, Ferreira AJ, Geuna S, Winter DA. Ankle kinematics to
evaluate functional recovery in crushed rat sciatic nerve. Muscle
Nerve. 2003;27:70614.
44. Li Y, Bickel KD, Im MJ, Hu L, Dellon AL, Vander Kolk C,
Manson PN. Effects of deferoxamine in ischemia/reperfusion injury
after peripheral nerve compression. Ann Plast Surg.
1996;36:3659.
45. Mau JL, Lin HC, Song SF. Antioxidant activity of several
specialty mushrooms. Food Res Int. 2002;35:51926.
46. Mau JL, Chang CN, Huang SJ, Chen CC. Antioxidant properties
of methanolic extracts from Grifola frondosa, Morchella esculenta
and Termitomyces albuminosus mycelia. Food Chem. 2004;87:1118.
47. Wong KH, Sabaratnam V, Abdullah N, Kuppusamy UR, Naidu M.
Effects of cultivation techniques and processing on antimicrobial
and antioxidant activities of Hericium erinaceus (Bull.:Fr.) Pers.
extracts. Food Technol Biotechnol. 2009;47:4755.
48. Azzouz M, Kennel PF, Warter J, Poindron P, Borg J.
Enhancement of mouse sciatic nerve regeneration by the long chain
fatty alcohol, n-hexacosanol. Exp Neurol. 1996;138:18097.
49. Ducker TB, Zeidman SM. Spinal cord injury. Role of steroid
therapy. Spine. 1994;19:22817.
50. Al-Bishri A, Dahlin R, Sunzel B, Rosenquist J. Systemic
betamethasone accelerates functional recovery after a crush injury
to rat sciatic nerve. J Oral Maxillofac Surg. 2005;63:9737.
51. Ding F, Cheng Q, Gu X. The repair effects of Achyranthes
bidentata extract on the crushed common peroneal nerve of rabbits.
Fitoterapia. 2008;79:1617.
Begell House Digital Library, http://dl.begellhouse.com
Downloaded 2009-10-14 from IP 71.255.84.142 by Maitake Products,
Inc